Interferon is a glycoprotein produced by the cells in response to viruses and some other agents named interferon inducers. Interferon possess antiviral and antitumor potential. It is presently used in clinical trials (#1).
There are two generally recognized classifications of interferon, i.e., according to the character of cells in which they are induced and according to the character of their inducer. In the former classification, fibroblast cells yield fibroblast interferon; leukocyte cells yield leukocyte interferon; and lymphoblastoid cells yield lymphoblastoid interferon. In the latter classification, any interferon induced by viruses or their nucleic acids or by synthetic inducers which in fact imitate the action of viral nucleic acids, e.g., synthetic analogue of double stranded RNA such as poly I:C, are named Type I interferon or viral interferon (independently of their producing cells). In addition to the foregoing, leukocytes were shown to produce another interferon named Type II interferon or immune interferon. Type II interferon is produced by sensitized leukocytes (from an immune animal including human) when induced by an antigen to which these leukocytes are sensitive. Non-sensitized leukocytes also produce Type II interferon when induced by certain non-viral agents such as various lectins, e.g., phytohemagglutinin (PHA) or Concanavallin A (CoA), or certain bacterial products, e.g., staphylococcal endotoxin A (SEA) (#2 and #3).
In summary, human leukocyte cells are capable of producing Type I interferon or Type II interferon. It appears that different kinds of lymphocytes are involved in the production of these Type I and Type II interferons. The Type I interferon is produced mainly by B cells whereas the Type II interferon is produced mainly by T cells. The Type I and Type II interferons differ in antigenicity. There is also a difference in their sensitivity to certain treatments. Type I interferon is stable over a wide acidic pH range (as low as about 2). On the other hand, Type II interferon is relatively pH unstable and is destroyed at a pH below about 4. The main feature which characterizes the Type I and the Type II interferons from practical point of view is that the Type II interferon was shown to possess considerably greater (up to 10 times) antitumor potential than is the case with the Type I interferon (#1). Of these two types of human leukocyte interferon only Type I (induced by Sendai virus) is presently used in clinical trails. The application of the highly active Type II interferon for clinical practice would offer obvious advantages.
Measles vaccine virus has been shown to be an effective interferon inducer of lymphoblastoid interferon (#4). The author focused on the ability of measles vaccine virus to multiply and to cause a persistent infection of the lymphoblastoid cells which are tumor-origin cells (#5). This permitted the elaboration of a model for the continuous production of lymphoblastoid interferon (#6). However, interferon induced by measles vaccine virus in lymphoblastoid cells is the usual Type I or viral interferon which does not differ from the Type I induced by the Sendai virus. Ion Gresser inoculated various leukocyte suspensions with Sendai virus, measles virus (Edmonston strain), and Polio I virus. The author reports that "after inoculation of the suspensions with either Sendai or measles virus, interferon in varying titers was detected in 21 of 22 preparations". Comparative high titer of at least 3072 is reported when Sendai virus is used as the virus. Low to essentially no titers are obtained using measles virus, namely (a) normal patient: titer at least 96 (to a maximum of 192); (b) congenital agammaglobulinemia patient: titer of 12. Leukocytes from two patients with measles rash in the absence of an added viral inducer gave no interferon titer after 3 and 7 days (#7).
One can conclude from Ion Gresser's experiments that measles virus possessed some interferon-inducing capacity, much inferior to the interferon-inducing capacity of Sendai virus. This fact apparently has not been lost sight of by subsequent researchers in the field in view of the fact that there apparently is a void in the state of the art with respect to further research on measles virus to induce interferon in leukocyte cells. On the other hand, a large body of interferon literature does indeed exist with respect to Sendai virus as an interferon inducer. Gresser did not disclose or appreciate the necessity of choosing measles sensitized leukocytes derived from a measle immune donor as the interferon-producing "factory" for the measles vaccine virus inducer. Gresser's disclosure reveals a lack of knowledge and/or appreciation that a natural mixture of Type I and Type II interferons can be induced from an in vitro medium comprising such measles sensitized leukocytes. It is not surprising, therefore, that Examples 2 and 12 of Table I of Gresser's article (#7, page 801) gave very low or relatively low interferon titers. Moreover, Examples 18 and 19 of Table I establish that presently sick, measles-infected donors (two) after 3 and 7 days did not produce interferon in vivo.